Phase I safety assessment of intrathecal injection of an american formulation of adenosine in humans

Abstract

Background: Preclinical studies of intrathecal adenosine suggest it may be effective in the treatment of acute and chronic pain in humans. A phase I safety trial of the intrathecal injection of a mannitol-containing formulation of adenosine in Sweden showed a considerable incidence of backache. We performed a phase I safety trial of intrathecal injection of the American formulation of adenosine, which lacks mannitol. Methods: Following US Food and Drug Administration and institutional review board approval and written informed consent, 65 volunteers were studied in two trials: an open-label, dose-escalating trial with intrathecal adenosine doses of 0.25-2.0 mg (25 subjects) and a double-blind, placebo-controlled trial of adenosine, 2 mg (40 subjects). Blood pressure, heart rate, end-tidal carbon dioxide, and sensory, motor, and reflex neurologic functions were systematically examined for 24 h after injection, and volunteers were contacted by telephone at times up to 6 months after injection. Results: Intrathecal adenosine did not affect blood pressure, heart rate, end-tidal carbon dioxide, or neurologic function. Headache was reported by 10 and back pain was reported by 8 of 30 subjects exposed to adenosine in the second double-blind trial, whereas none of these symptoms was reported by the 10 saline-treated subjects. Conclusion: These data support further investigation of intrathecal adenosine for analgesia in humans and suggest that this agent does not produce a high incidence of severe side effects.